Problem of sequence and fractionation in the clinical application of combined heat and radiation.

Tumor control, thermal enhancement, and therapeutic effect have been evaluated in a series of studies on 77 patients with a total of 163 multiple superficial lesions by using different protocols of combined radiotherapy and local external hyperthermia. Local tumor control and recurrence rate were constantly better in lesions treated with combined treatment in comparison with those treated with radiotherapy alone, regardless of treatment schedule. The enhancement of tumor control appeared to be related to both the magnitude of the applied heat and the size of radiation fractions, in that an increase in either produced an increase in tumor control. When tumor and critical normal tissue were heated to the same temperature, the immediate combination of heat and large radiation fractions resulted in a pronounced enhancement of tumor control, but the concomitantly heated normal tissue showed an increased percentage of radiation reaction, resulting in a low therapeutic advantage. By introducing an interval of 4 hr between the two modalities or by delivering few heat fractions during the course of a conventional fractionation radiotherapy, the enhancement of tumor control was lower, but the increase in skin reaction was minimal, resulting in a clearly improved therapeutic effect. When the tumor could be preferentially heated with respect to normal tissue, the immediate combination of the highest hyperthermic treatment and the largest radiation fractions resulted in the best therapeutic advantage, since no increase of skin reaction was observed.